NSAID Review

Question 1

Which of the following prostaglandins is released from endothelial tissue and has an anti-platelet effect (inhibits platelet adhesion, activation, and aggregation)?

A - Prostacyclin aka PGI2
B - Thromboxane A2 aka TXA2
C - Prostaglandin F2a aka PGF2a
D - Prostaglandin E2 aka PGE2

Answer 1

(A - PGI2)

Question 1

Which end product of the arachidonic acid pathway do NSAIDs block?

Answer 1

(Prostaglandins)

Question 2

Which of the following prostaglandins triggers vasoconstriction and platelet aggregation?

A - Prostacyclin aka PGI2
B - Thromboxane A2 aka TXA2
C - Prostaglandin F2a aka PGF2a
D - Prostaglandin E2 aka PGE2

Answer 2

(B - TXA2)

Question 3

Which of the following prostaglandins is a major proinflammatory and pain mediator, triggers vasodilation, decreases GI motility, and induces a fever?

A - Prostacyclin aka PGI2
B - Thromboxane A2 aka TXA2
C - Prostaglandin F2a aka PGF2a
D - Prostaglandin E2 aka PGE2

Answer 3

(D - PGE2)

Question 4

Which of the following prostaglandins triggers vasoconstriction, bronchoconstriction, and uterine and GI small muscle contractions?

A - Prostacyclin aka PGI2
B - Thromboxane A2 aka TXA2
C - Prostaglandin F2a aka PGF2a
D - Prostaglandin E2 aka PGE2

Answer 4

(C - PGF2a)

Question 5

Which of the following prostaglandins is primarily induced by COX-2?

A - Prostacyclin aka PGI2
B - Thromboxane A2 aka TXA2
C - Prostaglandin F2a aka PGF2a
D - Prostaglandin E2 aka PGE2

Answer 5

(D - PGE2)

Question 6

Which of the following prostaglandins is primarily induced by COX-1?

A - Prostacyclin aka PGI2
B - Thromboxane A2 aka TXA2
C - Prostaglandin F2a aka PGF2a
D - Prostaglandin E2 aka PGE2

Answer 6

(B - TXA2)

Question 7

What are some of the good things that PGE2 does?

Answer 7

(Promotes mucosal blood flow in the GIT and kidneys, maintains kidney fluid balance, and induces bronchodilation)

Question 8

Which of the prostaglandins are vasodilators?

Answer 8

(PGE2 and Prostacyclin/PGI2)

Question 9

Which of the prostaglandins are vasoconstrictors?

Answer 9

(PGF2 and thromboxane A2/TXA2)

Question 10

Which of the NSAIDs are the most COX-2 selective?

Answer 10

(Any drug that ends in coxib (firocoxib, robenacoxib, deracoxib), everything else is variable in COX-2 selectivity)

Question 11

COX-2 selective inhibitors are the safer choice particularly in healthy animals but can be less safe in patients with what types of underlying diseases?

Answer 11

(Renal, GI, or cardiovascular dzs)

Question 12

In general for NSAIDs…

• Oral bioavailability is low/moderate/high (choose).
• Volume of distribution is small/moderate/large (choose).
• Hepatic/renal (choose) elimination.

Answer 12

• Oral bioavailability is low/moderate/high (choose). (High)
• Volume of distribution is small/moderate/large (choose). (Small, high protein binding and though they have good lipophilicity, the high protein binding prevents CNS penetration)
• Hepatic/renal (choose) elimination. (Renal)

Question 13

Why are NSAIDs used for treatment of endotoxemia/sepsis?

Answer 13

(Bc prostaglandins are responsible for many of the clinical signs associated with endotoxemia/sepsis, they do not actually treat the toxin/bacteria)

Question 14

If you want to use an NSAID to aid in anticoagulation, what COX selectivity would you reach for?

Answer 14

(COX-1 selective drugs, bc remember than thromboxane is COX-1 induced and thromboxane = thrombus)

Question 15

What are the primary uses of NSAIDs?

Answer 15

(Antipyresis and tx pain by modulating inflammation)

Question 16

What are the two NSAID options for cats?

Answer 16

(Meloxicam and robenacoxib/onsior)

Question 17

What is the most common adverse effect of NSAIDs in dogs and cats which predictably tends to occur after 3-5 days of dosing?

Answer 17

(Gastritis leading to vomiting, diarrhea, and/or anorexia)

Question 18

How do the locations that dogs and cats vs. horses get GI ulcers compare?

Answer 18

(Dogs and cats → stomach and proximal small intestine; horses → stomach and right dorsal colon)

Question 19

How do NSAIDs cause GI ulcers?

Answer 19

(By inhibiting COX-2 and therefore inhibiting PGE2 which is necessary for healing pre-existing GI damage)

Question 20

Explain PG independent NSAID-induced stomach injury.

Answer 20

(NSAIDs are weak organic acids, when given orally they are non-ionized in gastric acid and become lipophilic, they then diffuse across the gastric mucosal epithelial cell membranes into the neutral cytoplasm where they are converted back into their ionized and hydrophilic form, drug is now trapped in the cell and accumulates leading to cell death)

Question 21

Why is the duodenum predisposed to NSAID related GI ulcers in dogs and cats?

Answer 21

(Bc of enterohepatic recycling, high concentrations of NSAIDs are secreted in the bile, bile is dumped into the duodenum; horses are spared from this bc they don’t have a gallbladder)

Question 22

Which NSAID is most associated with gastroduodenal perforations in dogs?

Answer 22

(Meloxicam)

Question 23

Which portions of the stomach in horses will have NSAID induced GI ulcers (i.e. if the ulcer is located in the other portion, it is likely not due to NSAIDs)?

Answer 23

(The glandular portion of the stomach is most affected by NSAID induced GI ulcers in horses, not the squamous portion)

Question 24

The decreased renal blood flow associated with blocking PGE2 and PGI2 are greatly exacerbated in patients with what issue?

Answer 24

(Dehydration bc they already have compromised renal blood flow)

Question 25

NSAID nephrotoxicity induces necrosis of what structures in the kidney?

Answer 25

(The medullary crest and the papilla, bc these structures normally receive less blood flow so they are more vulnerable to renal blood flow issues)

Question 26

As you increase the COX-1 selectively of the NSAID you are choosing to use, you are increasing the risk for thrombosis/bleeding (choose).

Answer 26

(Bleeding, bc by blocking COX-1, no thromboxane will be produced which causes thrombus formation, no thrombus = bleeding)

Question 27

You have a patient on an unknown COX selectivity NSAID who presented with a unilaterally cold forelimb paw (aka they threw a clot), you can surmise that the NSAID you gave is more COX-1/COX-2 (choose) selective.

Answer 27

(COX-2)

Question 28

(T/F) Idiosyncratic hepatotoxicity (anorexia, vomiting, icterus, hepatomegaly, increased bilirubin, ALT, ALP, AST) associated with NSAIDs is specific to carprofen.

Answer 28

(F, can occur with all NSAIDs although carprofen is the most implicated)

Question 29

What does phenylbutazone cause if it is administered perivascular?

Answer 29

(Severe tissue necrosis)

Question 30

Clostridial myositis is associated with IM injection of what NSAID in horses?

Answer 30

(Flunixin meglumine, even though it is labeled for this route of administration, do not use it!)

Question 31

(T/F) Injectable forms of phenylbutazone and flunixin meglumine can be given orally.

Answer 31

(T, taste like shit and causes mucosal irritation so mix with something tasty and rinse their mouth out after)

Question 32

How can you minimize adverse effects of NSAIDs?

Answer 32

(Dose appropriately (lowest effective dose, longest effective duration between doses), choose a drug labeled for the species you are working with, choose COX-2 selectives (safer but not entirely safe), and when provided use the dedicated dosing syringe; also don’t compound)

Question 33

What are some of the lab work tests that should be monitored regularly in animals regularly on NSAIDs?

Answer 33

(PCV/RBCs (all animals), total protein/albumin (horses), BUN/creatinine (all animals), liver enzymes (dogs, cats), and a UA (dogs, cats))